Wenbo Wang1, Linlin Zhao2, Zhenyu He3, Ning Wu4, Qiuxia Li5, Xinjian Qiu6, Lu Zhou7, Dongsheng Wang8. 1. Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China. Electronic address: wangwenbo@csu.edu.cn. 2. Physical Examination Center, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan, China. Electronic address: zllin7@126.com. 3. Institute of Traditional Chinese Medicine, Hunan University of Traditional Chinese Medicine, Changsha, 410208 Hunan, China. Electronic address: 412761859@qq.com. 4. Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China. Electronic address: 373840809@qq.com. 5. Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China. Electronic address: lqxlqx@csu.edu.cn. 6. Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China. Electronic address: qiuxjxy@126.com. 7. Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China. Electronic address: Zl1208@163.com. 8. Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China. Electronic address: wdsh666@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Ge-Gen-Jiao-Tai-Wan (GGJTW) formula, derived from traditional Chinese herbal medicine, is composed of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (Ge-Gen in Chinese), Coptis chinensis Franch (Huang-Lian), and Cinnamomum cassia (L.) J. Presl (Rou-Gui). GGJTW is used for treatment of diabetes in China, reflecting the potent hypoglycemic effect of its ingredients. However, little is known of the hypoglycemic effect of GGJTW and the underlying metabolic mechanism. AIM OF THE STUDY: This study aimed to investigate the hypoglycemic effect of GGJTW in type 2 diabetic rats and the metabolic mechanism of action. MATERIALS AND METHODS: Ultra high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomics approach was used for monitoring hyperglycaemia induced by high-sugar high-fat fodder and streptozotocin (STZ), and the protective effect of GGJTW. Dynamic fasting blood glucose (FBG) levels, body weight, and biochemical parameters, including lipid levels, hepatic-renal function, and hepatic histopathology were used to confirm the hyperglycaemic toxicity and attenuation effects. An orthogonal partial least squared-discriminant analysis (OPLS-DA) approach highlighted significant differences in the metabolome of the healthy control, diabetic, and drug-treated rats. The metabolomics pathway analysis (MetPA) and Kyoto encyclopedia of genes and genomes (KEGG) database were used to investigate the underlying metabolic pathways. RESULTS: Metabolic profiling revealed 37 metabolites as the most potential biomarker metabolites distinguishing GGJTW-treated rats from model rats. Most of the metabolites were primarily associated with bile acid metabolism and lipid metabolism. The most critical pathway was primary bile acid biosynthesis pathway involving the up-regulation of the levels of cholic acid (CA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodesoxycholic acid (TCDCA), and taurine. CONCLUSIONS: The significantly-altered metabolite levels indicated the hypoglycemic effect of GGJTW on diabetic rats and the underlying metabolic mechanism. This study will be meaningful for the clinical application of GGJTW and valuable for further exploration of the mechanism.
ETHNOPHARMACOLOGICAL RELEVANCE: Ge-Gen-Jiao-Tai-Wan (GGJTW) formula, derived from traditional Chinese herbal medicine, is composed of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (Ge-Gen in Chinese), Coptis chinensis Franch (Huang-Lian), and Cinnamomum cassia (L.) J. Presl (Rou-Gui). GGJTW is used for treatment of diabetes in China, reflecting the potent hypoglycemic effect of its ingredients. However, little is known of the hypoglycemic effect of GGJTW and the underlying metabolic mechanism. AIM OF THE STUDY: This study aimed to investigate the hypoglycemic effect of GGJTW in type 2 diabeticrats and the metabolic mechanism of action. MATERIALS AND METHODS: Ultra high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomics approach was used for monitoring hyperglycaemia induced by high-sugar high-fat fodder and streptozotocin (STZ), and the protective effect of GGJTW. Dynamic fasting blood glucose (FBG) levels, body weight, and biochemical parameters, including lipid levels, hepatic-renal function, and hepatic histopathology were used to confirm the hyperglycaemic toxicity and attenuation effects. An orthogonal partial least squared-discriminant analysis (OPLS-DA) approach highlighted significant differences in the metabolome of the healthy control, diabetic, and drug-treated rats. The metabolomics pathway analysis (MetPA) and Kyoto encyclopedia of genes and genomes (KEGG) database were used to investigate the underlying metabolic pathways. RESULTS: Metabolic profiling revealed 37 metabolites as the most potential biomarker metabolites distinguishing GGJTW-treated rats from model rats. Most of the metabolites were primarily associated with bile acid metabolism and lipid metabolism. The most critical pathway was primary bile acid biosynthesis pathway involving the up-regulation of the levels of cholic acid (CA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodesoxycholic acid (TCDCA), and taurine. CONCLUSIONS: The significantly-altered metabolite levels indicated the hypoglycemic effect of GGJTW on diabeticrats and the underlying metabolic mechanism. This study will be meaningful for the clinical application of GGJTW and valuable for further exploration of the mechanism.